This literature review is a compilation of the composition and, in most cases, the preparation instructions for simulated biological fluids that may be used as dissolution media in the evaluation of dissolution profiles and amount of drug released from pharmaceutical dosage forms. The use of simulated biological fluids can give a better understanding of the release mechanisms and possible in vivo behavior of a product and enhance the predictive capability of the dissolution testing. A summary of the major characteristics of the most used routes of administration that may affect dissolution and absorption of drug substances is presented. The routes and simulated biological fluids covered by this review are: • Parenteral: simulated body fluid and simulated synovial fluid. • Oral: fasted-state simulated gastric fluid, fed-state simulated gastric fluid, fasted-state simulated intestinal fluid, fed-state simulated intestinal fluid, simulated colonic fluid, fasted-state simulated colonic fluid, and fed-state simulated colonic fluid. • Buccal and sublingual: simulated saliva. • Pulmonary: simulated lung fluid. • Vaginal: simulated vaginal fluid and simulated semen. • Ophthalmic: simulated tears. Simulated sweat is also included. Some examples of how these simulated biological fluids are used to evaluate dosage forms are included in each route of administration. INTRODUCTION Until some decades ago, most of the conventional pharmaceutical dosage forms were essentially injections, oral formulations (solutions, suspensions, tablets, and capsules), topical creams, and ointments. With the progress of drug delivery technology, novel dosage forms have been developed to overcome the problems associated with conventional drug delivery. Research has been directed toward the use of alternatives to the parenteral route for drugs that cannot be delivered orally. Potential alternative portals of drug entry to the systemic circulation include buccal, sublingual, nasal, pulmonary, and vaginal routes, among others. These routes of administration are also used for the local delivery of drugs directly to the site of action, with consequent reduction in the dose needed to produce a pharmacological effect, eliminating problems related to first-pass metabolism and possibly minimizing systemic side effects (1). An important application of dissolution testing is the prediction of in vivo performance of pharmaceutical dosage forms. The media typically used for quality control dissolution testing do not represent all aspects of the physiological conditions of the most used routes of administration and do not allow correlation with in vivo data. Prediction of dosage form performance in the site where most of the absorption occurs requires adequate simulation of the in vivo conditions. This paper describes some characteristics of the parenteral, oral, buccal and sublingual, pulmonary, ophthalmic, and vaginal routes that are important to consider when developing simulated media. A compilation of the composition and preparation of several simulated biological fluids, including simulated sweat, with potential use as dissolution media is presented. PARENTERAL ROUTE The most used routes of injection are intramuscular, intravenous, and subcutaneous and are normally associated with short-term effects. Novel implant devices that can adequately control drug release and provide a prolonged duration of effect have been developed (1). To evaluate the in vitro drug release from these dosage forms, the dissolution medium should have ion concentrations almost equal to those of the human plasma. Table 1 describes the ionic composition of simulated body fluid (SBF) and human blood plasma. Simulated body fluid was developed initially to evaluate the surface structural changes of glass-ceramics used to manufacture artificial vertebrae, ileum, tooth roots (2), and bioactive material used to repair hard tissues such as artificial middle-ear bone and maxillofacial implants (3). This simulated body fluid was prepared using the reagents listed in Table 2. These reagents were added to 700 mL of water in the order given in Table 2, one by one, after each reagent was completely dissolved. The pH was adjusted to 7.4 with 1 M *Corresponding author. diss-18-03-03.indd 15 8/31/2011 3:22:15 PM dx.doi.org/10.14227/DT180311P15

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Simulated Biological Fluids with Possible Application in Dissolution Testing

Spectrometric Identification of Organic Compounds

Review of Disintegrants and the Disintegration Phenomena.

Oral films: Current status and future perspectives: I - Galenical development and quality attributes.

Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition.

Coprocessed superdisintegrant consisting of crospovidone and SSG exhibited good flow and compression characteristics. Cefixime trihydrate and ibuprofen tablets containing coprocessed superdisintegrant exhibited quick disintegration and improved drug dissolution.

Preparation and assessment of novel coprocessed superdisintegrant consisting of crospovidone and sodium starch glycolate: a technical note.

The coprocessed superdisintegrant proved to be superior to the physical blend in terms of flow due to size enlargement. Furthermore, the coprocessed superdisintegrant displayed superiority in terms of crushing strength, disintegration time, and drug dissolution. The advantages of the proposed method are easy adaptability in industry and the possibility of bypassing the existing patents in the ereas of quick disintegration and dissolution.

Improving the tablet characteristics and dissolution profile of ibuprofen by using a novel coprocessed superdisintegrant: a technical note.

Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken design: In vitro, ex vivo, in vivo and human studies.

The present investigation was undertaken to fabricate modified release tablet of metoprolol succinate using hydroxypropyl methylcellulose (HPMC) and xanthan gum as a matrixing agent. A 32 full factorial design was employed for the optimization of formulation. The percentage drug released at a given time (Y60, Y240 and Y720) and the time required for a given percentage of drug to be released (t50%) were selected as dependent variables. The in vitro drug dissolution study was carried out in pH 6.8 phosphate buffer employing paddle rotated at 50 rpm. The similarity factor (f2) was calculated for selection of best batch considering mean in vitro dissolution data of Seloken® XL as a reference profile. It is concluded that the desired drug release pattern can be obtained by using a proper combination of HPMC (high gelling ability) and xanthan gum (quick gelling tendency). The economy of xanthan gum and faster hydration rate favors its use in modified release tablets. The matrix integrity during dissolution testing was maintained by using hydroxypropyl methylcellulose.

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Fabrication of Modified Release Tablet Formulation of Metoprolol Succinate using Hydroxypropyl Methylcellulose and Xanthan Gum

Metformin hydrochloride exhibits poor compressibility during compaction, often resulting in weak and unacceptable tablets with a high tendency to cap. The purpose of this study was to develop directly compressible metformin hydrochloride by the spray-drying technique in the presence of polymer. Metformin hydrochloride was dissolved in solutions containing a polymer, namely polyvinylpyrrolidone (PVP K30), in various concentrations ranging from 0-3% (m/V). These solutions were employed for spray-drying. Spray-dried drug was evaluated for yield, flow property and compressibility profile. Metformin hydrochloride spray-dried in the presence of 2% PVP K30 showed an excellent flow property and compressibility profile. From the calculated Heckel's parameter (Py = 2.086), it was demonstrated that the treated drug showed better particle arrangement in the initial compression stage. Kawakita analysis revealed better packability of the treated drug compared to the untreated drug. Differential scanning calorimetry and Fourier transform infrared spectroscopy experiments showed that the spray-dried drug did not undergo any chemical modifications. Tablets made from the spray-dried drug (90%, m/m) were evaluated for crushing strength, friability and disintegration time and the results were found satisfactory.

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Rajesh K. Parikh

Papers

Preparation and assessment of novel coprocessed superdisintegrant consisting of crospovidone and sodium starch glycolate: a technical note.

Improving the tablet characteristics and dissolution profile of ibuprofen by using a novel coprocessed superdisintegrant: a technical note.

Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken design: In vitro, ex vivo, in vivo and human studies.

Fabrication of Modified Release Tablet Formulation of Metoprolol Succinate using Hydroxypropyl Methylcellulose and Xanthan Gum

Development of directly compressible metformin hydrochloride by the spray-drying technique.